Likely inborn error of metabolism

Gene: ALG14

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval

Created: 3 Mar 2022, 12:59 p.m. | Last Modified: 3 Mar 2022, 12:59 p.m.

Panel Version: 2.223

There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 9 Jul 2020, 12:14 p.m. | Last Modified: 9 Jul 2020, 12:14 p.m.

Panel Version: 2.15

Comment on list classification: Associated with Myasthenic syndrome, congenital, 15, without tubular aggregates 616227 in OMIM, but not associated with phenotype in Gen2Phen. At least 6 variants reported in at least 5 cases with varying phenotypes. PMID 23404334 reports compound heterozygous (p.P65L, P.R104*) sibs, who manifested with myasthenic syndromes, but did not have intellectural disability nor seizures and were 62 and 51 years old when reported. PMID 28733338 reports two compound heterozygous (p.D74N, pV141G), (p.D74N, p.R109Q) cases and a homozygous (p.D74N), with early and lethal neurodegeneration with myasthenic and myopathic features, but the cases died before intellectual disability was manifiest. However, seizures were evident in two compound heterozygous families. PMID 30221345 reports a homozygous splicing variant in a case with intellectual disability and seizures. Functional studies were presented showing that this variant resulting in exon skipping, however, this was not completely prenetrant as wild type protein was detected at a low level in the patient.

Created: 9 Jul 2020, 12:11 p.m. | Last Modified: 9 Jul 2020, 12:11 p.m.

Panel Version: 2.14

Associated with phenotype in OMIM, not in G2P / DD. At least 2 variants reported in 2 sisters

Created: 23 Feb 2017, 5:11 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Myasthenic syndrome, congenital, 15, without tubular aggregates 616227

Publications

• 27604308
• 23404334